Emodin ameliorates diabetic neuropathic pain through inhibiting up-regulation of TRPV1 and pro-inflammatory cytokines in dorsal root ganglions in rats

@#Background & Objective: Peripheral neuropathy is one of the most common complications of diabetes and leads to sensory symptoms, including diabetic neuropathic pain (DNP). Emodin has potential analgesic effect for the treatment of pain-related diseases. However, the analgesic effect of emodin on DNP and its possible mechanism remains unknown. The aim of the present study is to investigate the effect of emodin on STZ-induced DNP in rats and its potential molecular mechanism. Methods: To determine the analgesic effect of emodin on DNP, a mouse model of STZ-induced DNP was established. The pain-related behaviors were evaluated by von Frey test, and hot plate test. The mRNA and protein expression of several TRP channels was detected by qRT-PCR and western blot methods, and the level of inflammatory cytokines was determined by ELISA. Results: The mechanical and thermal pain thresholds were significantly decreased in DNP rats. A single injection of emodin treatment significantly reduced DNP. Further results demonstrated that emodin inhibited the up-regulation of Trpv1 mRNA in the DRG of DNP rats. Our data also indicated that emodin significantly reduced the levels of TNF-α, IL-1β and IL-6 in the DRG of DNP rats. Conclusions: Emodin ameliorates mechanical allodynia and thermal hyperalgesia in DNP rats by down-regulating the expression of TRPV1 in DRG and the expression of TNF-α, IL-1β and IL-6. Emodin serves as a potent analgesic reagent for treatment and prevention of DNP.

Expression of MiRNA-19a in Cells of Multiple Myeloma Patients and Its Effect on the Characteristics of Myeloma Cells / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To detect the expression level of miR-19a, one of the oncogenic miR-17-92 cluster, in multiple myeloma cell lines Lp-1 and U266 in vitro and to explore the effects of miR-19a on biological behavior, such as proliferation, migration and apoptosis of Lp-1 and U266 myeloma cells by transfection with miR-19a mimic through Lipofectamine2000.</p><p><b>METHODS</b>The reverse transcription-PCR was applied to detect the expression level of miR-19a in multiple myeloma cell lines Lp-1 and U266 in vitro. The CCK8 was used to assay the effect of miR-19a on the proliferation of Lp-1 and U266 cells in vitro, the transwell migration test was adopted to determine the effect of up-regulation of miR-19a on the migration of Lp-1 and U266 multiple myeloma cells in vitro. The flow cytometry was used to detect the effect of miR-19a on the apoptosis of Lp-1 and U266 cells in vitro.</p><p><b>RESULTS</b>The miR-19a expression was higher in Lp-1 and U266 multiple myeloma cells; compared with the transfected cells with a specific miR-19a NC, those samples transfected with miR-19a mimic displayed significantly higher expression of miR-19a (P<0.05), indicating a higher transfection efficiency; the miR-19a could promote the proliferation of Lp-1 and U266 multiple myeloma cells in vitro. MiR-19a could promote migration ability of Lp-1 and U266 multiple myeloma cell lines in vitro and could inhibit the apoptosis of Lp-1 and U266 cells.</p><p><b>CONCLUSION</b>miR-19a is overexpressed significantly in Lp-1 and U266 multiple myeloma cells, and promots the proliferation and invasion of the myeloma cells, but inhibits their apoptosis.</p>

Population pharmacokinetic study of biapenem in critical patients / 中国药学杂志

OBJECTIVE: To research population pharmacokinetics of biapenem in critical patients after repeated dosing. METHODS: Blood samples were collected according to the different time points after intravenous administration of 300 mg for many times in the group of critical patients. High-performance liquid chromatography (HPLC) was used to determine the drug concentration in plasma.And pharmacokinetic parameters was caculated. RESULTS: The main pharmacokinetic parameters for critical patients were as follows: ρmax was (6.66±2.93)mg·L-1, Tmax was (0.51±0.04) h, AUC0-∞ was (18.98±16.95) mg·h·L-1, T1/2 was (2.06±1.93) h, Cl was (20.9±17.4) L·h-1, Vd was (46.43±3.5) L. CONCLUSION: The pharmacokinetic parameters of biapenem in critical patients with a significant difference was found in healthy people. So need according to pharmacokinetic characteristics of patients to develop personalized anti-infection plan.

The effects of prenatal stress on the cell apoptosis after MCAO in adult offspring rats / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To evaluate the effects of prenatal stress on neurological functions after middle cerebral artery occlusion (MCAO) in adult offspring rats.</p><p><b>METHODS</b>Pregnant rats were randomly assigned to prenatal stress treatment, which was exposed to restraint three times daily in the last week of pregnancy, and no prenatal stress treatment. Adult male offspring rats were subjected to transient focal cerebral ischemia by MCAO. They were randomly divided into four groups: sham group, prenatal stress + sham group, MCAO group and prenatal stress + MCAO group (n = 10). After 24 hours of reperfusion, the neurological deficits were evaluated. The infarct size, cell apoptosis and expression of Caspase 3, cleaved Caspase 3 and Bcl-2 were detected.</p><p><b>RESULTS</b>Compared with MCAO group, the neurological deficits, infarct size and apoptotic cells in prenatal stress + MCAO group were increased significantly (all P < 0.05). The expressions of Caspase 3 and cleaved Caspase 3 were much greater in prenatal stress + MCAO group than those of MCAO group, while the expression of Bcl-2 was significantly decreased in prenatal stress + MCAO group compared with MCAO group (all P < 0.05).</p><p><b>CONCLUSION</b>Prenatal stress might exacerbate neuroloeical deficits in the offspring rats after MCAO by increasing cell apoptosis.</p>

Mitochondrial DNA Haplogroups and the Risk of Sporadic Parkinson's Disease in Han Chinese / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Mitochondrial dysfunction is linked to the pathogenesis of Parkinson's disease (PD). However, the precise role of mitochondrial DNA (mtDNA) variations is obscure. On the other hand, mtDNA haplogroups have been inconsistently reported to modify the risk of PD among different population. Here, we try to explore the relationship between mtDNA haplogroups and sporadic PD in a Han Chinese population.</p><p><b>METHODS</b>Nine single-nucleotide polymorphisms, which define the major Asian mtDNA haplogroups (A, B, C, D, F, G), were detected via polymerase chain reaction-restriction fragment length polymorphism or denaturing polyacrylamide gel electrophoresis in 279 sporadic PD patients and 510 matched controls of Han population.</p><p><b>RESULTS</b>Overall, the distribution of mtDNA haplogroups did not show any significant differences between patients and controls. However, after stratification by age at onset, the frequency of haplogroup B was significantly lower in patients with early-onset PD (EOPD) compared to the controls (odds ratio [OR] =0.225, 95% confidence interval [CI]: 0.082-0.619, P = 0.004), while other haplogroups did not show significant differences. After stratification by age at examination, among subjects younger than 50 years of age: Haplogroup B also showed a lower frequency in PD cases (OR = 0.146, 95% CI: 0.030-0.715, P = 0.018) while haplogroup D presented a higher risk of PD (OR = 3.579, 95% CI: 1.112-11.523, P = 0.033), other haplogroups also did not show significant differences in the group.</p><p><b>CONCLUSIONS</b>Our study indicates that haplogroup B might confer a lower risk for EOPD and people younger than 50 years in Han Chinese, while haplogroup D probably lead a higher risk of PD in people younger than 50 years of age. In brief, particular Asian mtDNA haplogroups likely play a role in the pathogenesis of PD among Han Chinese.</p>

Factors influencing clinical outcomes of acute ischemic stroke treated with intravenous recombinant tissue plasminogen activator / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Thrombolysis with recombinant tissue plasminogen activator (rt-PA) has gained international recognition, clinical outcomes following this thrombolytic therapy varied from patient to patient. Factors affecting clinical outcomes have not been well understood yet, so this retrospective case-control study aimed to investigate factors that may influence clinical outcomes of acute ischemic stroke treated with intravenous rt-PA.</p><p><b>METHODS</b>One hundred and one patients with acute ischemic stroke who received intravenous rt-PA thrombolysis within 4.5 hours from disease onset were included. Patients were divided into good or poor outcome group according to modified Rankin Scale (mRS) score, good outcome group: mRS score of 0-1; poor outcome group: mRS of 2-6. Stroke characteristics were compared between the two groups. Factors for stroke outcomes were analyzed via univariate analysis and Logistic regression.</p><p><b>RESULTS</b>Of the 101 patients studied, patients in good outcome group (n = 55) were significantly younger than patients in poor outcome group (n = 46, (62.82 ± 14.25) vs. (68.81 ± 9.85) years, P = 0.029). Good outcome group had fewer patients with diabetic history (9.09% vs. 28.26%, P = 0.012), fewer patients with leukoaraiosis (7.27% vs. 28.26%, P = 0.005) and presented with lower blood glucose level ((5.72 ± 1.76) vs. (6.72 ± 1.32) mmol/L, P = 0.012), lower systolic blood pressure level ((135.45 ± 19.36) vs. (148.78 ± 19.39) mmHg, P = 0.003), lower baseline NIHSS score (12.02 ± 5.26 vs. 15.78 ± 4.98, P = 0.002) and shorter onset-to-treatment time (OTT) ((2.38 ± 1.21) vs. (2.57 ± 1.03) hours, P = 0.044) than poor outcome group. Logistic regression analysis showed that absence of diabetic history (odds ratio (OR) 0.968 (95% CI 0.941-0.996)), absence of leukoaraiosis (OR 0.835 (95% CI 0.712-0.980)), lower baseline NIHSS score (OR 0.885 (95% CI 0.793-0.989)), lower pre-thrombolysis systolic blood pressure (OR 0.962 (95% CI 0.929-0.997)), and lower blood glucose level (OR 0.699 (95% CI 0.491-0.994)) before thrombolysis were significantly associated with better outcome.</p><p><b>CONCLUSION</b>Patients with no history of diabetes, no leukoaraiosis, low blood glucose level, low systolic blood pressure level and low baseline NIHSS score before thrombolysis have a better outcome.</p>